CA2710061C - Rhoc-based immunotherapy - Google Patents
Rhoc-based immunotherapy Download PDFInfo
- Publication number
- CA2710061C CA2710061C CA2710061A CA2710061A CA2710061C CA 2710061 C CA2710061 C CA 2710061C CA 2710061 A CA2710061 A CA 2710061A CA 2710061 A CA2710061 A CA 2710061A CA 2710061 C CA2710061 C CA 2710061C
- Authority
- CA
- Canada
- Prior art keywords
- seq
- rhoc
- vaccine composition
- hla
- peptide fragment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000009169 immunotherapy Methods 0.000 title description 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 291
- 108010033276 Peptide Fragments Proteins 0.000 claims abstract description 136
- 102000007079 Peptide Fragments Human genes 0.000 claims abstract description 136
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 125
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 122
- 201000011510 cancer Diseases 0.000 claims abstract description 79
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 77
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 60
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 54
- 208000037819 metastatic cancer Diseases 0.000 claims abstract description 37
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims abstract description 37
- 238000011282 treatment Methods 0.000 claims abstract description 37
- 230000028993 immune response Effects 0.000 claims abstract description 23
- 230000002163 immunogen Effects 0.000 claims abstract description 22
- 235000001014 amino acid Nutrition 0.000 claims description 198
- 150000001413 amino acids Chemical class 0.000 claims description 185
- 239000000203 mixture Substances 0.000 claims description 129
- 229960005486 vaccine Drugs 0.000 claims description 126
- 210000004027 cell Anatomy 0.000 claims description 110
- 125000000539 amino acid group Chemical group 0.000 claims description 71
- 239000002671 adjuvant Substances 0.000 claims description 63
- 235000018102 proteins Nutrition 0.000 claims description 50
- 230000004044 response Effects 0.000 claims description 43
- 108010086377 HLA-A3 Antigen Proteins 0.000 claims description 38
- 239000000427 antigen Substances 0.000 claims description 36
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 35
- 108091007433 antigens Proteins 0.000 claims description 34
- 102000036639 antigens Human genes 0.000 claims description 34
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 claims description 32
- 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 claims description 29
- 101150111584 RHOA gene Proteins 0.000 claims description 29
- 210000004443 dendritic cell Anatomy 0.000 claims description 27
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 26
- 238000006467 substitution reaction Methods 0.000 claims description 26
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 24
- 150000007523 nucleic acids Chemical class 0.000 claims description 24
- 108091054437 MHC class I family Proteins 0.000 claims description 22
- 101150054980 Rhob gene Proteins 0.000 claims description 22
- 230000003902 lesion Effects 0.000 claims description 22
- 239000013598 vector Substances 0.000 claims description 21
- 108020004707 nucleic acids Proteins 0.000 claims description 20
- 102000039446 nucleic acids Human genes 0.000 claims description 20
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 claims description 19
- 239000000126 substance Substances 0.000 claims description 17
- 102000043129 MHC class I family Human genes 0.000 claims description 16
- 235000004279 alanine Nutrition 0.000 claims description 16
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical group CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 15
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Chemical group CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 15
- 210000000265 leukocyte Anatomy 0.000 claims description 15
- 238000011510 Elispot assay Methods 0.000 claims description 14
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 13
- 238000000338 in vitro Methods 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 10
- 108010074032 HLA-A2 Antigen Proteins 0.000 claims description 10
- 102000025850 HLA-A2 Antigen Human genes 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 230000002265 prevention Effects 0.000 claims description 9
- 102000004127 Cytokines Human genes 0.000 claims description 8
- 108090000695 Cytokines Proteins 0.000 claims description 8
- 238000011065 in-situ storage Methods 0.000 claims description 8
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 claims description 7
- 108010058607 HLA-B Antigens Proteins 0.000 claims description 7
- 231100000433 cytotoxic Toxicity 0.000 claims description 7
- 230000001472 cytotoxic effect Effects 0.000 claims description 7
- 239000002246 antineoplastic agent Substances 0.000 claims description 6
- 230000007423 decrease Effects 0.000 claims description 6
- 230000012010 growth Effects 0.000 claims description 6
- 108010035452 HLA-A1 Antigen Proteins 0.000 claims description 5
- 230000001580 bacterial effect Effects 0.000 claims description 5
- 238000001514 detection method Methods 0.000 claims description 5
- 230000001939 inductive effect Effects 0.000 claims description 5
- 239000004094 surface-active agent Substances 0.000 claims description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 4
- 108010013476 HLA-A24 Antigen Proteins 0.000 claims description 4
- 108010004141 HLA-B35 Antigen Proteins 0.000 claims description 4
- 108010091938 HLA-B7 Antigen Proteins 0.000 claims description 4
- 108010039075 HLA-B8 Antigen Proteins 0.000 claims description 4
- 210000003162 effector t lymphocyte Anatomy 0.000 claims description 4
- 230000003308 immunostimulating effect Effects 0.000 claims description 4
- 230000036961 partial effect Effects 0.000 claims description 4
- 108010036972 HLA-A11 Antigen Proteins 0.000 claims description 3
- 108010021736 HLA-B15 Antigen Proteins 0.000 claims description 3
- 108010061486 HLA-B27 Antigen Proteins 0.000 claims description 3
- 102000012153 HLA-B27 Antigen Human genes 0.000 claims description 3
- 108010014597 HLA-B44 Antigen Proteins 0.000 claims description 3
- 238000002512 chemotherapy Methods 0.000 claims description 3
- 238000001415 gene therapy Methods 0.000 claims description 3
- 229920001184 polypeptide Polymers 0.000 claims description 3
- 230000003612 virological effect Effects 0.000 claims description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims description 2
- 108020000946 Bacterial DNA Proteins 0.000 claims description 2
- 108010075326 HLA-B51 Antigen Proteins 0.000 claims description 2
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 claims description 2
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 claims description 2
- 230000024932 T cell mediated immunity Effects 0.000 claims description 2
- 230000008595 infiltration Effects 0.000 claims description 2
- 238000001764 infiltration Methods 0.000 claims description 2
- 238000001959 radiotherapy Methods 0.000 claims description 2
- 230000004936 stimulating effect Effects 0.000 claims description 2
- 239000013603 viral vector Substances 0.000 claims description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims 1
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 claims 1
- 238000002255 vaccination Methods 0.000 abstract description 10
- 238000003745 diagnosis Methods 0.000 abstract description 5
- 238000001727 in vivo Methods 0.000 abstract description 4
- 238000002560 therapeutic procedure Methods 0.000 abstract description 4
- 230000001093 anti-cancer Effects 0.000 abstract description 3
- 238000004393 prognosis Methods 0.000 abstract description 2
- 238000011321 prophylaxis Methods 0.000 abstract description 2
- 229940024606 amino acid Drugs 0.000 description 164
- 201000001441 melanoma Diseases 0.000 description 32
- 238000000034 method Methods 0.000 description 30
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 23
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 23
- 230000014509 gene expression Effects 0.000 description 21
- 210000004899 c-terminal region Anatomy 0.000 description 19
- 238000003556 assay Methods 0.000 description 17
- 108091008874 T cell receptors Proteins 0.000 description 16
- 238000012546 transfer Methods 0.000 description 16
- 101000755496 Canis lupus familiaris Transforming protein RhoA Proteins 0.000 description 14
- 125000003275 alpha amino acid group Chemical group 0.000 description 14
- 210000001519 tissue Anatomy 0.000 description 14
- -1 Leu Chemical group 0.000 description 13
- 206010027476 Metastases Diseases 0.000 description 13
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 12
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 12
- 230000005867 T cell response Effects 0.000 description 11
- 239000012634 fragment Substances 0.000 description 11
- 230000009401 metastasis Effects 0.000 description 11
- 239000008194 pharmaceutical composition Substances 0.000 description 11
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 10
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 10
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 10
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 10
- 108010002350 Interleukin-2 Proteins 0.000 description 9
- 102000000588 Interleukin-2 Human genes 0.000 description 9
- 206010033128 Ovarian cancer Diseases 0.000 description 9
- 210000004881 tumor cell Anatomy 0.000 description 9
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 8
- 206010061535 Ovarian neoplasm Diseases 0.000 description 8
- 238000007792 addition Methods 0.000 description 8
- 230000009089 cytolysis Effects 0.000 description 8
- 238000002649 immunization Methods 0.000 description 8
- 206010006187 Breast cancer Diseases 0.000 description 7
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 7
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 7
- 208000006265 Renal cell carcinoma Diseases 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 230000006698 induction Effects 0.000 description 7
- 230000001394 metastastic effect Effects 0.000 description 7
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 6
- 208000026310 Breast neoplasm Diseases 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 102000011786 HLA-A Antigens Human genes 0.000 description 6
- 108010075704 HLA-A Antigens Proteins 0.000 description 6
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 6
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 6
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 6
- 208000032839 leukemia Diseases 0.000 description 6
- 230000000670 limiting effect Effects 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 206010061289 metastatic neoplasm Diseases 0.000 description 6
- 230000002269 spontaneous effect Effects 0.000 description 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
- 108700028369 Alleles Proteins 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 5
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 5
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 201000010536 head and neck cancer Diseases 0.000 description 5
- 208000014829 head and neck neoplasm Diseases 0.000 description 5
- 210000000987 immune system Anatomy 0.000 description 5
- 238000011068 loading method Methods 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 208000037821 progressive disease Diseases 0.000 description 5
- 101150079354 rho gene Proteins 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 230000006641 stabilisation Effects 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 239000004475 Arginine Substances 0.000 description 4
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 4
- 101800001318 Capsid protein VP4 Proteins 0.000 description 4
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 4
- 206010009944 Colon cancer Diseases 0.000 description 4
- 239000004214 Fast Green FCF Substances 0.000 description 4
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 4
- 108091006109 GTPases Proteins 0.000 description 4
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 4
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 102000042463 Rho family Human genes 0.000 description 4
- 102100027609 Rho-related GTP-binding protein RhoD Human genes 0.000 description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 description 4
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 4
- 206010017758 gastric cancer Diseases 0.000 description 4
- 239000004120 green S Substances 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 239000004407 iron oxides and hydroxides Substances 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 208000020816 lung neoplasm Diseases 0.000 description 4
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 102000007268 rho GTP-Binding Proteins Human genes 0.000 description 4
- 108010033674 rho GTP-Binding Proteins Proteins 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000011105 stabilization Methods 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 201000011549 stomach cancer Diseases 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 239000004149 tartrazine Substances 0.000 description 4
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 4
- 230000005951 type IV hypersensitivity Effects 0.000 description 4
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 description 3
- 108010072335 HLA-A19 antigen Proteins 0.000 description 3
- 108010052199 HLA-C Antigens Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 0.000 description 3
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 3
- 108010058846 Ovalbumin Proteins 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 108091078243 Rho family Proteins 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000006037 cell lysis Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 206010022000 influenza Diseases 0.000 description 3
- 229960000310 isoleucine Drugs 0.000 description 3
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 229940092253 ovalbumin Drugs 0.000 description 3
- 230000004481 post-translational protein modification Effects 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000013823 prenylation Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 229930182490 saponin Natural products 0.000 description 3
- 150000007949 saponins Chemical class 0.000 description 3
- 238000002864 sequence alignment Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 230000009258 tissue cross reactivity Effects 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- BEJKOYIMCGMNRB-GRHHLOCNSA-N (2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-amino-3-phenylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 BEJKOYIMCGMNRB-GRHHLOCNSA-N 0.000 description 2
- 201000003076 Angiosarcoma Diseases 0.000 description 2
- 206010003571 Astrocytoma Diseases 0.000 description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
- 206010004146 Basal cell carcinoma Diseases 0.000 description 2
- 206010004593 Bile duct cancer Diseases 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- 101800001415 Bri23 peptide Proteins 0.000 description 2
- 208000011691 Burkitt lymphomas Diseases 0.000 description 2
- 101800000655 C-terminal peptide Proteins 0.000 description 2
- 102400000107 C-terminal peptide Human genes 0.000 description 2
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 208000005243 Chondrosarcoma Diseases 0.000 description 2
- 201000009047 Chordoma Diseases 0.000 description 2
- 208000006332 Choriocarcinoma Diseases 0.000 description 2
- 208000009798 Craniopharyngioma Diseases 0.000 description 2
- 238000009007 Diagnostic Kit Methods 0.000 description 2
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 2
- 206010014733 Endometrial cancer Diseases 0.000 description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 description 2
- 206010014967 Ependymoma Diseases 0.000 description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
- 208000006168 Ewing Sarcoma Diseases 0.000 description 2
- 201000008808 Fibrosarcoma Diseases 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- 108010068567 HLA-Cw1 antigen Proteins 0.000 description 2
- 208000001258 Hemangiosarcoma Diseases 0.000 description 2
- 208000017604 Hodgkin disease Diseases 0.000 description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- 206010023825 Laryngeal cancer Diseases 0.000 description 2
- 208000018142 Leiomyosarcoma Diseases 0.000 description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 102000043131 MHC class II family Human genes 0.000 description 2
- 108091054438 MHC class II family Proteins 0.000 description 2
- 208000007054 Medullary Carcinoma Diseases 0.000 description 2
- 208000000172 Medulloblastoma Diseases 0.000 description 2
- 206010027406 Mesothelioma Diseases 0.000 description 2
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000003445 Mouth Neoplasms Diseases 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- 206010061309 Neoplasm progression Diseases 0.000 description 2
- 206010029260 Neuroblastoma Diseases 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
- 201000010133 Oligodendroglioma Diseases 0.000 description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 208000007641 Pinealoma Diseases 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 208000033759 Prolymphocytic T-Cell Leukemia Diseases 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 208000015634 Rectal Neoplasms Diseases 0.000 description 2
- 201000000582 Retinoblastoma Diseases 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 201000010208 Seminoma Diseases 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 208000026651 T-cell prolymphocytic leukemia Diseases 0.000 description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 description 2
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 2
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 208000002495 Uterine Neoplasms Diseases 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 2
- 208000008383 Wilms tumor Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 208000017733 acquired polycythemia vera Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- IADUEWIQBXOCDZ-UHFFFAOYSA-N azetidine-2-carboxylic acid Chemical compound OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 description 2
- 201000007180 bile duct carcinoma Diseases 0.000 description 2
- 201000001531 bladder carcinoma Diseases 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 2
- 238000009566 cancer vaccine Methods 0.000 description 2
- 229940022399 cancer vaccine Drugs 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000010307 cell transformation Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000007969 cellular immunity Effects 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 230000001461 cytolytic effect Effects 0.000 description 2
- 230000003436 cytoskeletal effect Effects 0.000 description 2
- 210000004292 cytoskeleton Anatomy 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 208000037828 epithelial carcinoma Diseases 0.000 description 2
- 201000004101 esophageal cancer Diseases 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 201000009277 hairy cell leukemia Diseases 0.000 description 2
- 208000025750 heavy chain disease Diseases 0.000 description 2
- 201000002222 hemangioblastoma Diseases 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 230000001024 immunotherapeutic effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 206010023841 laryngeal neoplasm Diseases 0.000 description 2
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 206010024627 liposarcoma Diseases 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 201000005296 lung carcinoma Diseases 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 2
- 210000002752 melanocyte Anatomy 0.000 description 2
- 206010027191 meningioma Diseases 0.000 description 2
- 208000021039 metastatic melanoma Diseases 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 208000001611 myxosarcoma Diseases 0.000 description 2
- 208000025189 neoplasm of testis Diseases 0.000 description 2
- 208000007538 neurilemmoma Diseases 0.000 description 2
- 231100001083 no cytotoxicity Toxicity 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229960003104 ornithine Drugs 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 2
- 201000010198 papillary carcinoma Diseases 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229940023041 peptide vaccine Drugs 0.000 description 2
- 230000002688 persistence Effects 0.000 description 2
- 208000024724 pineal body neoplasm Diseases 0.000 description 2
- 201000004123 pineal gland cancer Diseases 0.000 description 2
- 208000037244 polycythemia vera Diseases 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 206010038038 rectal cancer Diseases 0.000 description 2
- 201000001275 rectum cancer Diseases 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
- 201000008407 sebaceous adenocarcinoma Diseases 0.000 description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 201000010965 sweat gland carcinoma Diseases 0.000 description 2
- 206010042863 synovial sarcoma Diseases 0.000 description 2
- 229960003080 taurine Drugs 0.000 description 2
- 201000003120 testicular cancer Diseases 0.000 description 2
- 230000002992 thymic effect Effects 0.000 description 2
- 201000002510 thyroid cancer Diseases 0.000 description 2
- 239000000439 tumor marker Substances 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 239000007762 w/o emulsion Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 description 1
- FPJGLSZLQLNZIW-VIFPVBQESA-N (2s)-2-amino-3-(4-methyl-1h-indol-3-yl)propanoic acid Chemical compound CC1=CC=CC2=C1C(C[C@H](N)C(O)=O)=CN2 FPJGLSZLQLNZIW-VIFPVBQESA-N 0.000 description 1
- YHQZWWDVLJPRIF-JLHRHDQISA-N (4R)-4-[[(2S,3R)-2-[acetyl-[(3R,4R,5S,6R)-3-amino-4-[(1R)-1-carboxyethoxy]-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]amino]-3-hydroxybutanoyl]amino]-5-amino-5-oxopentanoic acid Chemical compound C(C)(=O)N([C@@H]([C@H](O)C)C(=O)N[C@H](CCC(=O)O)C(N)=O)C1[C@H](N)[C@@H](O[C@@H](C(=O)O)C)[C@H](O)[C@H](O1)CO YHQZWWDVLJPRIF-JLHRHDQISA-N 0.000 description 1
- KJTLQQUUPVSXIM-ZCFIWIBFSA-M (R)-mevalonate Chemical compound OCC[C@](O)(C)CC([O-])=O KJTLQQUUPVSXIM-ZCFIWIBFSA-M 0.000 description 1
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 1
- 108010042708 Acetylmuramyl-Alanyl-Isoglutamine Proteins 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 241000272478 Aquila Species 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- IADUEWIQBXOCDZ-VKHMYHEASA-N Azetidine-2-carboxylic acid Natural products OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 108010075254 C-Peptide Proteins 0.000 description 1
- 108091007381 CBL proteins Proteins 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010049048 Cholera Toxin Chemical class 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 102000005927 Cysteine Proteases Human genes 0.000 description 1
- 108010005843 Cysteine Proteases Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 description 1
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
- UQBOJOOOTLPNST-UHFFFAOYSA-N Dehydroalanine Chemical compound NC(=C)C(O)=O UQBOJOOOTLPNST-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102100035273 E3 ubiquitin-protein ligase CBL-B Human genes 0.000 description 1
- 102100034214 E3 ubiquitin-protein ligase RNF128 Human genes 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102100036242 HLA class II histocompatibility antigen, DQ alpha 2 chain Human genes 0.000 description 1
- 102100036241 HLA class II histocompatibility antigen, DQ beta 1 chain Human genes 0.000 description 1
- 102100040505 HLA class II histocompatibility antigen, DR alpha chain Human genes 0.000 description 1
- 108010032218 HLA-A*23 antigen Proteins 0.000 description 1
- 108010089211 HLA-A*25 antigen Proteins 0.000 description 1
- 108010080347 HLA-A*26 antigen Proteins 0.000 description 1
- 108010041379 HLA-A*30 antigen Proteins 0.000 description 1
- 108010026122 HLA-A*33 antigen Proteins 0.000 description 1
- 108010020404 HLA-A*43 antigen Proteins 0.000 description 1
- 108010020515 HLA-A*68 antigen Proteins 0.000 description 1
- 108010079897 HLA-A10 antigen Proteins 0.000 description 1
- 108010029526 HLA-A28 antigen Proteins 0.000 description 1
- 108010034115 HLA-A29 antigen Proteins 0.000 description 1
- 108010018475 HLA-A31 antigen Proteins 0.000 description 1
- 108010052046 HLA-A9 antigen Proteins 0.000 description 1
- 108010002668 HLA-B12 antigen Proteins 0.000 description 1
- 108010009256 HLA-B13 Antigen Proteins 0.000 description 1
- 108010087017 HLA-B14 Antigen Proteins 0.000 description 1
- 108010013698 HLA-B17 antigen Proteins 0.000 description 1
- 108010075646 HLA-B18 Antigen Proteins 0.000 description 1
- 108010057606 HLA-B21 antigen Proteins 0.000 description 1
- 108010083104 HLA-B22 antigen Proteins 0.000 description 1
- 108010070087 HLA-B37 Antigen Proteins 0.000 description 1
- 108010086707 HLA-B38 Antigen Proteins 0.000 description 1
- 108010042972 HLA-B39 Antigen Proteins 0.000 description 1
- 108010087480 HLA-B40 Antigen Proteins 0.000 description 1
- 108010014398 HLA-B42 antigen Proteins 0.000 description 1
- 108010028938 HLA-B45 antigen Proteins 0.000 description 1
- 108010076685 HLA-B46 antigen Proteins 0.000 description 1
- 108010022839 HLA-B47 antigen Proteins 0.000 description 1
- 108010058038 HLA-B5 antigen Proteins 0.000 description 1
- 108010016670 HLA-C*02 antigen Proteins 0.000 description 1
- 108010070768 HLA-C*03 antigen Proteins 0.000 description 1
- 108010069149 HLA-C*04 antigen Proteins 0.000 description 1
- 108010016121 HLA-C*05 antigen Proteins 0.000 description 1
- 108010059045 HLA-C*06 antigen Proteins 0.000 description 1
- 108010007655 HLA-C*70 antigen Proteins 0.000 description 1
- 108010086786 HLA-DQA1 antigen Proteins 0.000 description 1
- 108010065026 HLA-DQB1 antigen Proteins 0.000 description 1
- 108010067802 HLA-DR alpha-Chains Proteins 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101000737265 Homo sapiens E3 ubiquitin-protein ligase CBL-B Proteins 0.000 description 1
- 101000711673 Homo sapiens E3 ubiquitin-protein ligase RNF128 Proteins 0.000 description 1
- 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 description 1
- 101000578784 Homo sapiens Melanoma antigen recognized by T-cells 1 Proteins 0.000 description 1
- 101100518359 Homo sapiens RHO gene Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000800133 Homo sapiens Thyroglobulin Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 101100209954 Human papillomavirus type 16 L1 gene Proteins 0.000 description 1
- 101000767631 Human papillomavirus type 16 Protein E7 Proteins 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 208000005726 Inflammatory Breast Neoplasms Diseases 0.000 description 1
- 206010021980 Inflammatory carcinoma of the breast Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100040019 Interferon alpha-1/13 Human genes 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 102000003812 Interleukin-15 Human genes 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- DWPCPZJAHOETAG-IMJSIDKUSA-N L-lanthionine Chemical compound OC(=O)[C@@H](N)CSC[C@H](N)C(O)=O DWPCPZJAHOETAG-IMJSIDKUSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- ZFOMKMMPBOQKMC-KXUCPTDWSA-N L-pyrrolysine Chemical compound C[C@@H]1CC=N[C@H]1C(=O)NCCCC[C@H]([NH3+])C([O-])=O ZFOMKMMPBOQKMC-KXUCPTDWSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 241000194036 Lactococcus Species 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 206010050017 Lung cancer metastatic Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102100029450 M1-specific T cell receptor alpha chain Human genes 0.000 description 1
- 206010064912 Malignant transformation Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 1
- 102100028389 Melanoma antigen recognized by T-cells 1 Human genes 0.000 description 1
- 108010071463 Melanoma-Specific Antigens Proteins 0.000 description 1
- 102000007557 Melanoma-Specific Antigens Human genes 0.000 description 1
- 102000018656 Mitogen Receptors Human genes 0.000 description 1
- 108010052006 Mitogen Receptors Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100346932 Mus musculus Muc1 gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- PIJXCSUPSNFXNE-QRZOAFCBSA-N N-acetyl-4-(N-acetylglucosaminyl)muramoyl-L-alanyl-D-isoglutamine Chemical compound OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@@H]1[C@@H](NC(C)=O)[C@H](O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 PIJXCSUPSNFXNE-QRZOAFCBSA-N 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- 101150097297 Nedd4 gene Proteins 0.000 description 1
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 108010001441 Phosphopeptides Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108091036414 Polyinosinic:polycytidylic acid Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 101710093543 Probable non-specific lipid-transfer protein Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 102000055251 Proto-Oncogene Proteins c-cbl Human genes 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108700025832 Serum Response Element Proteins 0.000 description 1
- 102000000763 Survivin Human genes 0.000 description 1
- 108010002687 Survivin Proteins 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102000009843 Thyroglobulin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 208000035896 Twin-reversed arterial perfusion sequence Diseases 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- UZQJVUCHXGYFLQ-AYDHOLPZSA-N [(2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-4-[(2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-6-(hy Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)CC(O)[C@]1(CCC(CC14)(C)C)C(=O)O[C@H]1[C@@H]([C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZQJVUCHXGYFLQ-AYDHOLPZSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- NWMHDZMRVUOQGL-CZEIJOLGSA-N almurtide Chemical compound OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)CO[C@@H]([C@H](O)[C@H](O)CO)[C@@H](NC(C)=O)C=O NWMHDZMRVUOQGL-CZEIJOLGSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- 208000030270 breast disease Diseases 0.000 description 1
- 230000009400 cancer invasion Effects 0.000 description 1
- 125000001314 canonical amino-acid group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000011393 cytotoxic chemotherapy Methods 0.000 description 1
- 231100000050 cytotoxic potential Toxicity 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 229960002986 dinoprostone Drugs 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 238000011331 genomic analysis Methods 0.000 description 1
- 229910001679 gibbsite Inorganic materials 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000009851 immunogenic response Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000002480 immunoprotective effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 201000004653 inflammatory breast carcinoma Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 230000006122 isoprenylation Effects 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 210000001865 kupffer cell Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000036212 malign transformation Effects 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- DWPCPZJAHOETAG-UHFFFAOYSA-N meso-lanthionine Natural products OC(=O)C(N)CSCC(N)C(O)=O DWPCPZJAHOETAG-UHFFFAOYSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- JMUHBNWAORSSBD-WKYWBUFDSA-N mifamurtide Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCC)COP(O)(=O)OCCNC(=O)[C@H](C)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)OC(O)[C@@H]1NC(C)=O JMUHBNWAORSSBD-WKYWBUFDSA-N 0.000 description 1
- 229960005225 mifamurtide Drugs 0.000 description 1
- 108700007621 mifamurtide Proteins 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 230000016379 mucosal immune response Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- 210000002241 neurite Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 102000027450 oncoproteins Human genes 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 108010082406 peptide permease Proteins 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 125000001151 peptidyl group Chemical group 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940115272 polyinosinic:polycytidylic acid Drugs 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000001855 preneoplastic effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000000275 quality assurance Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000012121 regulation of immune response Effects 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000010845 search algorithm Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229940055619 selenocysteine Drugs 0.000 description 1
- ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 1
- 235000016491 selenocysteine Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 102000030938 small GTPase Human genes 0.000 description 1
- 108060007624 small GTPase Proteins 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960000814 tetanus toxoid Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 229960002175 thyroglobulin Drugs 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001154—Enzymes
- A61K39/001164—GTPases, e.g. Ras or Rho
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464454—Enzymes
- A61K39/464464—GTPases, e.g. Ras or Rho
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/82—Translation products from oncogenes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the cancer treated
- A61K2239/57—Skin; melanoma
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y306/00—Hydrolases acting on acid anhydrides (3.6)
- C12Y306/05—Hydrolases acting on acid anhydrides (3.6) acting on GTP; involved in cellular and subcellular movement (3.6.5)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Genetics & Genomics (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Hematology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA200701844 | 2007-12-19 | ||
| DKPA200701844 | 2007-12-19 | ||
| PCT/DK2008/050324 WO2009076966A2 (en) | 2007-12-19 | 2008-12-18 | Rhoc-based immunotherapy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2710061A1 CA2710061A1 (en) | 2009-06-25 |
| CA2710061C true CA2710061C (en) | 2022-07-12 |
Family
ID=59270757
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2710061A Active CA2710061C (en) | 2007-12-19 | 2008-12-18 | Rhoc-based immunotherapy |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US9163077B2 (es) |
| EP (1) | EP2234635B1 (es) |
| JP (3) | JP2011506497A (es) |
| AU (1) | AU2008338063B2 (es) |
| CA (1) | CA2710061C (es) |
| DK (1) | DK2234635T3 (es) |
| ES (1) | ES2623447T3 (es) |
| PL (1) | PL2234635T3 (es) |
| WO (1) | WO2009076966A2 (es) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2234635T3 (en) * | 2007-12-19 | 2017-05-01 | Rhovac Aps | RhoC-based immunotherapy |
| US10019634B2 (en) * | 2010-06-04 | 2018-07-10 | Masoud Vaziri | Method and apparatus for an eye tracking wearable computer |
| EP3294311A4 (en) * | 2015-03-05 | 2018-12-19 | Amrita Therapeutics Limited | A modified peptide as an anticancer agent |
| AU2018365800A1 (en) | 2017-11-08 | 2020-04-02 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for treating cancer using RHOA dominant negative forms |
| KR101947452B1 (ko) * | 2018-04-26 | 2019-02-13 | 주식회사 에스와이테크 | 하이브리드 acp 시스템 및 그 제조방법 |
| KR200488051Y1 (ko) * | 2018-05-28 | 2018-12-07 | 주식회사 에스와이테크 | 완충 z-바 |
| WO2022017895A1 (en) | 2020-07-21 | 2022-01-27 | Rhovac Aps | Treatment of residual disease |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001526914A (ja) | 1997-12-31 | 2001-12-25 | インサイト・ファーマスーティカルズ・インコーポレイテッド | ヒト・調節タンパク質 |
| US6814968B1 (en) | 1998-06-04 | 2004-11-09 | Vanderbilt University | Inhibition of viral infection and spread with viral and RhoA-derived peptides |
| US20030039635A1 (en) * | 1998-09-30 | 2003-02-27 | Corixa Corporation | Compositions and methods for WT1 specific immunotherapy |
| WO2001041815A2 (en) * | 1999-12-10 | 2001-06-14 | Whitehead Institute For Biomedical Research | Metastasis genes and uses thereof |
| CA2425648A1 (en) * | 2000-10-19 | 2002-04-19 | Epimmune Inc. | Hla class i and ii binding peptides and their uses |
| CA2881568C (en) * | 2000-10-27 | 2019-09-24 | Novartis Vaccines And Diagnostics, Inc. | Nucleic acids and proteins from streptococcus groups a & b |
| WO2003008537A2 (en) | 2001-04-06 | 2003-01-30 | Mannkind Corporation | Epitope sequences |
| US7194802B2 (en) * | 2002-03-26 | 2007-03-27 | Seagate Technology Llc | Tool for certifying a head-gimbal assembly |
| DE10217035A1 (de) | 2002-04-11 | 2004-01-22 | Universitätsklinikum Charité Medizinische Fakultät der Humboldt-Universität Akademische Verwaltung - Forschung | Rekrutierungsmodule von RhoA und RhoC |
| US7417026B2 (en) * | 2003-08-13 | 2008-08-26 | Children's Hospital Medical Center | Mobilization of hematopoietic cells |
| US7960100B1 (en) * | 2004-04-30 | 2011-06-14 | Celera Corporation | Colon cancer targets and uses thereof |
| US7763418B2 (en) * | 2005-07-05 | 2010-07-27 | Cytoskeleton, Inc. | Detection of Rho proteins |
| DK2234635T3 (en) * | 2007-12-19 | 2017-05-01 | Rhovac Aps | RhoC-based immunotherapy |
-
2008
- 2008-12-18 DK DK08862897.9T patent/DK2234635T3/en active
- 2008-12-18 ES ES08862897.9T patent/ES2623447T3/es active Active
- 2008-12-18 AU AU2008338063A patent/AU2008338063B2/en active Active
- 2008-12-18 JP JP2010538345A patent/JP2011506497A/ja active Pending
- 2008-12-18 WO PCT/DK2008/050324 patent/WO2009076966A2/en active Application Filing
- 2008-12-18 CA CA2710061A patent/CA2710061C/en active Active
- 2008-12-18 PL PL08862897T patent/PL2234635T3/pl unknown
- 2008-12-18 US US12/808,649 patent/US9163077B2/en active Active
- 2008-12-18 EP EP08862897.9A patent/EP2234635B1/en active Active
-
2014
- 2014-02-17 JP JP2014027157A patent/JP5813801B2/ja active Active
-
2015
- 2015-09-16 JP JP2015182828A patent/JP6084671B2/ja active Active
- 2015-09-24 US US14/863,691 patent/US20160008448A1/en not_active Abandoned
-
2019
- 2019-04-19 US US16/389,676 patent/US20190247480A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| DK2234635T3 (en) | 2017-05-01 |
| JP2011506497A (ja) | 2011-03-03 |
| US9163077B2 (en) | 2015-10-20 |
| PL2234635T3 (pl) | 2017-08-31 |
| JP2014139185A (ja) | 2014-07-31 |
| JP2016014043A (ja) | 2016-01-28 |
| US20110002954A1 (en) | 2011-01-06 |
| JP6084671B2 (ja) | 2017-02-22 |
| ES2623447T3 (es) | 2017-07-11 |
| JP5813801B2 (ja) | 2015-11-17 |
| CA2710061A1 (en) | 2009-06-25 |
| EP2234635A2 (en) | 2010-10-06 |
| WO2009076966A2 (en) | 2009-06-25 |
| US20190247480A1 (en) | 2019-08-15 |
| AU2008338063A1 (en) | 2009-06-25 |
| AU2008338063B2 (en) | 2013-03-14 |
| WO2009076966A3 (en) | 2009-08-20 |
| US20160008448A1 (en) | 2016-01-14 |
| EP2234635B1 (en) | 2017-01-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20190247480A1 (en) | RhoC-Based Immunotherapy | |
| AU2004290866B2 (en) | Proteins belonging to the BcL-2 family and fragments thereof, and their use in cancer patients | |
| DK2119726T4 (en) | Novel and powerful MHC class II peptides derived from survivin and neurocan | |
| US9687539B2 (en) | CD4+ T survivin epitopes and uses thereof | |
| US20080107668A1 (en) | Cytotoxic t-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer | |
| WO2009036246A2 (en) | Immunogens that induce cytotoxic t-lymphocytes and their use in prevention, treatment, and diagnosis of cancer | |
| US9475841B2 (en) | Melanoma antigen peptide and uses thereof | |
| ANDERSEN et al. | Patent 2710061 Summary | |
| US20150291660A1 (en) | Novel melanoma antigen peptide and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20131010 |
|
| EEER | Examination request |
Effective date: 20131010 |